The present inention relates to novel pharmaceutical compositions based on essential fatty acids (E.F.A.), for dermal use which exhibit prolonged and continuous action.
It is now universally acceptable, particularly since the work of BURR [J. Biol. Chem. 82 p. 342-345 (1929)] that the E.F.A.'s are indispensible for the animal kingdom and that their deficiency is involved in the appearance of dermatological lesions in man and in the animal. Immature or severed rats which are subjected to a lipidless diet exhibit poor growth, a squamous skin, a loss of fur and premature death. In other words, the rats show pathological picture as a result of a lipidless diet. The addition of E.F.A.'s and particularly the addition of linoleic and arachidonic acid to their diet prevents these symptoms. On the other hand, the addition of saturated and mono-unsaturated fatty acids has no effect.
In the dog, the deficiency results in the appearance of a cutaneous dryness and a slight depilation. Then, it is manifested by a desquamation and an exzema which gradually becomes generalised from the abdomen.
At present it is accepted that linoleic acid takes part as a structural element in the membranal phospholipids of the cells. It occurs in a form esterified at the .beta. position on the glycerol portion of these compounds. The presence of linoleic acid plays an important role in the integrity of the skin barrier. It avoids transepidermal loss of moisture.
The role of arachidonic acid and of homo .gamma. linoleic acid is quite different. These molecules come into action as prostaglandin precursors:
arachidonic acid (20:4 w 6) is the precursor of all prostaglandins with two double bonds; PA0 homo .gamma. linoleic acid (20:3 w 6) is the precursor of all prostaglandins with one double bond. PA0 essential fatty acids (E.F.A.)--5 to 35% of the total weight--on a suitable solid macromolecular support; PA0 diffusion regulators or the active components; PA0 stabilisers for the plastics material serving as the support, and PA0 E.F.A. stablising agents.
The animal organism is not capable of synthesising these E.F.A.'s. In fact, dehydrogenases capable of creating a new double bond at w 6 or at w 3 do not exist in the animal world (they do, however, exist, in vegetables).
This enzymatic lack which is limited to a single biochemical step, prevents the synthesis of polyunsaturated E.F.A's of the two series w 6 and w 3. In addition, it prevents, from w 3 E.F.A.'s, the synthesis of w 6 E.F.A.'s and vice versa.
It is necessary to supply w 3 and w 6 E.F.A.'s at the same time to the animal. In mammals, it is particularly the w 6 E.F.A.'s which are important.
This synthetic defect and the biological importance of these molecules oblige the animal to find in its environment, sources of E.F.A.'s.
Two entry routes for these compounds into the organism exist: the digestive tract and the skin. It was BUTCHER (Journ. of Investig. Dermatology 16/1/1973 p. 43-48) who showed that linoleic acid passes rapidly through the skin barrier, penetrates into the cells of the epidermis and reaches the cutaneous capillaries. However after several years of treatment and tens of thousands of applications, practioners have observed that the local application of high doses of E.F.A.'s is contra-indicated, because it results very frequently in an appreciable increase in the growth of the cells of the dermis.
It is the objective of the present invention to avoid this very troublesome drawback. It is also an objective of the present invention to provide a novel pharmaceutical preparation with prolonged and regulated action over time which is superior to other preparations containing E.F.A.'s, such as ointments, creams and lotions. It should also be appreciated that pharmacological and clinical advantages are realized by the continuous release of active substances for a prolonged period of the pharmaceutical preparations of the present invention.